Lung transplantation is the treatment of choice for end-stage lung disease, but survival after lung transplant remains disappointingly low. Acute rejection episodes put lung grafts at greater risk of failing. However, acute rejection is often clinically silent and difficult to detect by any means other than biopsy, which requires an invasive procedure. Therefore, noninvasive methods for detecting and quantifying the presence of acute rejection could potentially improve outcomes for lung transplant recipients by improving our ability to detect acute rejection that requires treatment. Because T cells must proliferate in the lungs to cause acute rejection, we propose using the novel positron emission tomography (PET) tracer [18F]ISO-1, which targets the proliferation marker sigma-2 receptor, also recently characterized as the progesterone receptor membrane component-1 (PGRMC1), to image T cell activation in lung grafts. We have shown that PET imaging with [18F]fluorodeoxyglucose ([18F]FDG) also detects acute rejection and can measure its response to treatment; therefore, we will evaluate the ability of [18F]ISO-1 and [18F]FDG to detect acute rejection in a novel mouse model of left lung transplantation and in human lung transplant recipients.